BEE 4530 - 2022 Student Papers

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    Modeling NK Cell Toxin Diffusion
    Bryan, Michaela; McLane, Liam; Park, Andy; Tjokorda, Indira (2022-05-27)
    Natural killer (NK) cells are a key part of the body’s innate immune system, killing cells that have been damaged or stressed by infection and controlling the spread of disease while a slower, more powerful adaptive immune response can be prepared. They accomplish this by the controlled release of potent mediators of cell death like granzyme B, as well as the pore-forming perforin molecules that allow them to pass through target cell membranes. NK cells’ ability to destroy other host cells has made them a focus of much research into fighting cancer and microbial infections; however, this same potential for harm also necessitates a delicate system of regulation that must be interacted with carefully to minimize collateral damage to healthy host tissue. This study seeks to understand the movement of the granzyme B and perforin released from an NK cell using COMSOL Multiphysics 5.5, and ultimately to assess and quantify nearby cellular death. Granzyme B and perforin movement, transformation, and accumulation were modeled by mass transfer physics that accounted for reactions, diffusion, and partitioning across cell membranes. We assumed a cubical computational domain containing spherical subdomains: an NK cell, a target cell, and bystander cells. Some key model parameters are the amount of granzyme B and perforin released, their diffusion rates in different domains, their degradation rate constants, and the minimum lethal quantity of granzyme B. Damage to the cell was defined as reaching a threshold of granzyme B accumulation concentration inducing apoptosis, or cell death. The current literature suggests that extracellular concentrations in the picomolar range are sufficient to cause apoptosis [1], from which an estimate of lethal intracellular concentration was derived. We used two different models, one in which the NK cell attaches itself to a damaged cell and releases toxins asymmetrically, and another in which the NK cell is free-floating, and releases toxin uniformly across its surface. For each model, we randomized the cell locations and averaged the effects found in each scenario. This random distribution reflects the unordered arrangement of cells in vivo and provided a more refined perspective into bystander cell death. Modulation of NK cell activation can help us understand diffusion from a non-convergent release and its feasibility in clearing pathological cells while minimizing damage to healthy cells. Using the non-converged model, we found the concentration of toxin throughout the system at large and calculated cell death. We found that, across all five configurations of cells, less than 5% of the bystander cells were killed by the NK cell and the target cell was always killed. We thus concluded that the NK cell mechanism, even for non-converged release, works as intended and kills its target with little collateral damage. We were also able to discover important mechanisms in this system with relevance to genetic engineering of NK cells, perforin, and granzyme B.We found that the molecule count of granzyme B and perforin was highly effective in changing the concentration of internalized granzyme B, especially in comparision to changing the diffusivity through the extracellular fluid. A higher granzyme B diffusivity resulted in reduced granzyme internalization, which allows us to conclude that the two species reaching the cells at the same time is more important for their function than for one species to move to the cells very quickly.
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    How do Laser Pointers Damage your Retina?
    Lee, Joseph; Kuhikar, Sneha; van der Vliet, Riemer (2022-05-27)
    Lasers are devices used for many applications, for instance, in CD burning and reading, to baffle an audience in a light show or to point out details on a projector. The handheld laser or laser pointer is not given much thought, never mind that it could be seen as a dangerous object. And although the vast majority of market-available laser pointers are completely safe and even carry a warning, incidents occur. Goofing children or adults are seriously hurt due to over exposure to a laser device into their eyes, causing vision impairment that can last for life. Although your eyes provide some natural protection against intense flashes of light, such as the blinking reflex, damage can occur before this sets in. Additionally, a person can be unaware that damage is being inflicted onto the retinal region of their eyes and therefore continue looking into the laser. In some scenarios, the label on the laser does not correspond to the actual power of a laser and therefore it can be hard to know what lasers are safe and for which laser you need protective gear. In this project, we will be exploring damage caused by a visible spectrum laser to the retina of a human eye. We will investigate the thresholds of time and laser power before thermal damage to the retina is caused. To this end, we will be using a 2D axisymmetric model of the retina undergoing heating through a laser at a fixed point. We will be analyzing several factors that can determine the extent of thermal damage to the retina and will analyze different wavelengths or colors of visible spectrum laser light. Through changing parameters, we have found that wider beams are safer compared to more narrow beams as the power output of these lasers is less condensed. Furthermore, it is shown that power is linearly proportional to the heating of the retinal region. Additionally it is shown that cornea thickness, which is related to age, as elderly people tend to have thinner corneal regions, is not a significant factor in retinal damage. The visible wavelengths considered in this project did not significantly influence the heating of the fovea. The FDA has clear guidelines regarding laser power and as shown by the model in this paper these are justified as power is a clear indicator of danger and high powered lasers should be handled with caution. However, as shown in this project, the laser diameter, or waist, is also an important factor in laser safety and should be considered more carefully when designing or distributing laser devices.
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    Optimizing Nitrogen Fertilizer Quantities in Cereal Crop Root Systems to Minimize Leaching
    Kuelbs, Chloe; Liu, Jiren; Sadoff, Hunter; Shen, Jeffrey (2022-05-27)
    Loss of nitrogen due to leaching is one of the most pressing issues in agriculture as it leads to excessive crop production costs and pollution. N leaching contributes to atmospheric and aquatic pollution [1]. The production of nitrogen fertilizers accounts for 3% of worldwide natural gas consumption and contributes to 3% of global greenhouse gas emissions. Fertilizer leaching accounts for 23 trillion grams of nitrogen loss per year [2]. Understanding resource capture in cereal root systems provides yield and production data useful for environmental and economic efficiency. Thus, there is already considerable research on modeling water and N uptake by root systems. There are general models that describe uptake with root length density over the course of a season [3]. There are also a variety of existing models used to simulate mineral movement in soil systems that have been adapted to model N leaching in crop root systems, including DRAINMOD, DSSAT, N_ABLE, and EPIC [4]. We aim to model the consumption of nitrogen by cereal crop roots, as well as leaching under topsoil fertilizer placement in order to optimize the amount of fertilizer needed. An optimized amount of fertilizer will maximize plant uptake while minimizing the amount leached in the soil. It will save farmers money while minimizing ecological impact. We will model the nitrogen distribution and absorption over a set amount of time. During this length of time, rainfall will occur at certain periods in order to mimic real environmental conditions. In order to accurately model the top-down system, we must first simulate the uptake of the fertilizer into the water during rainfall. We model our system as 2D axisymmetric. We will describe our system using mass transfer equations representing the convective flow, transient uptake and dispersion over time under known initial concentrations and dispersive constants. We then use fluid flow equations to model the traversal of water through the soil/root system. The absorption of the water and N by the plant is a function of the root density, for which the equations are known. Using this information in simulation, we will be able to model how much nitrogen is absorbed by the root system as well as how much is leached beyond the boundaries of the crop. We found that most root uptake of nitrogen occurs in the top-most region which was expected. N uptake also increases as root length density increases. We plotted total N flow and uptake against time and found that only 30.3% of initial nitrogen was absorbed by the plant over the course of 90 days. Additionally, our water content and matric potential are validated using a study by Wu et. al. in which matric potential, h, and water content, θ, were measured 5 days after an irrigation event [5]. We modeled our precipitation to match their field conditions. We plotted our matric potential with respect to depth into the soil layer and our water content with respect to depth against the Wu et. al. results. The trend of our model matches that of the measured values with reasonable precision. Our matric potential with respect to depth plot rendered an R2 value of 0.766 and our plot of water content with respect to depth achieved an R2 of 0.937 (Fig. 12 & 13).
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    Hydrogel Smart Bandage as a Diagnostic Tool for Infection in Burn Wounds
    Kelly, Abby; Zhai, Mattieu; Li, Alan; Zhu, Jiaming (2022-05-27)
    Every year, almost half a million people are admitted to the emergency room because of burn wounds. Of the thousands of deaths that result from these wounds, more than half are due to complications from infection. An easy solution would be to administer antibiotics immediately, but this can lead to serious problems. When antibiotics are given, the majority of bacteria die, but a few with natural resistances may survive. These cells will eventually grow and reproduce, leading to the formation of bacterial cell lines that are resistant to current antibiotics. Currently, detection of infection requires evaluation by a medical professional to avoid taking antibiotics unnecessarily. Unfortunately, this method is very time consuming and may take several days to obtain test results such as blood or bacterial cultures. This option also may not be accessible in developing countries. Since infection can be fatal, it is beneficial to have a way to determine if a wound is infected without the need to visit a doctor and wait for test results. Here, we describe a smart hydrogel bandage that is able to detect when a burn wound has become infected. We chose to model a hydrogel bandage designed by SmartWound PREDICT using COMSOL, a finite element analysis simulation software. This bandage consists of a thin block of agarose hydrogel. This block contains wells that hold lipid vesicles full of fluorescent dye. The dye is self-quenching, meaning that the dye will not fluoresce while it is present in large concentrations within the minute volume of the vesicle. Once the vesicles rupture, the concentration will decrease as the dye exits the vesicle, allowing the dye to fluoresce. After a burn wound has occurred, the hydrogel bandage is placed over it. When the wound becomes colonized by bacteria (such that the immune system alone is insufficient in fending off the infection and medical intervention is required), the bacteria begin producing the pore-forming toxin alpha hemolysin (⍺-H). This toxin diffuses up through the bottom of the bandage and into the vesicle-containing wells. Upon contact with the ⍺-H, the vesicles will lyse and release the dye, which will begin to fluoresce in the presence of UV light. The fluorescence will signify that the wound has become infected and that the wearer should seek medical treatment. Our model investigates potential methods to minimize the time for fluorescent dye to be released after infection and maximize the time before the dye comes into contact with the skin. We want to be able to detect the presence of an infection quickly without allowing the dye to contaminate the wound. Because the safety data sheet recommends washing skin thoroughly with soap and water upon contact with the dye, we hope to minimize skin contact with the dye in our design. We based our bandage design on the preexisting bandage designed by SmartWound. To validate our model, we compared our COMSOL model results to the results obtained with the SmartWound PREDICT bandage. We found that our bandage exhibited visible fluorescence after 4 hours, like theirs did. We also found a similar dye concentration in the bandage after a set period of time. The validation did require altering some of our model parameters to reflect the fact that we modeled a typical wound and they tested their bandage on a bacterial biofilm, but any changes that were made were numerical and did not alter the integrity of the model. To nvestigate the effects of geometry, we also tested several slightly different bandage designs as well. Based on the information gathered from our model, we can make several recommendations about potential improvements in bandage design. First, we recommend that the vesicle wells should have a lower concentration of vesicles. This would make the bandage less expensive to produce without changing how long it takes for the bandage to fluoresce after being placed in contact with an infected wound. Decreasing the agarose concentration of the hydrogel bandage would be another potential improvement because it also would contribute to decreasing the cost of the bandage. It is important to note, however, that decreasing the percentage of agarose would also affect the mechanical properties of the bandage. This is beyond the scope of our model, but it may be an important factor to consider. A third potential improvement to the bandage would be to change the type of dye contained in the vesicles. If the current dye (6-carboxyfluorescein) was replaced with a larger dye (like sulforhodamine B), it would take longer to reach the skin after being released from the vesicles. This alteration could contribute to lowering the risk that the wound will be contaminated with dye. Another significant benefit of sulforhodamine B is that it is stable at room temperature, unlike 6-carboxyfluorescein that must be refrigerated for long-term storage. This would allow the sulforhodamine B based bandage to be more accessible in developing countries. The drawback to this dye is that it is significantly more expensive than 6-carboxyfluorescein. This expense could be offset in part by the decrease in the concentration of vesicles in the well; if there are fewer vesicles there will be less dye to pay for. Infection in burn wounds kills thousands of people every year. A bandage that informs its user when the wound is infected could drastically decrease the mortality rate, while also being a more convenient and accessible method for detecting infection.
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    Victoria’s Secret Problem: Heat Loss in Mastectomy Patients
    Chen, Hsin Huei; Irons, Kelly; Lee, Taehee; Mathur, Shubham (2022-05-27)
    Mastectomies are performed to treat or prevent the risk of breast cancer. Annually, over 100,000 women in the US undergo some form of mastectomy [1]. Approximately 40% of women who undergo mastectomies elect to undergo breast reconstruction surgery [2]. Tissue removal during mastectomy decreases insulation and breast reconstruction has been shown to be associated with relatively permanent decreased touch and temperature sensibility at the skin. As a result of these factors, patients are susceptible to thermal injury when attempting to warm their breasts, sometimes even leading to partial and full thickness burns. The objective of this study was to determine the fabric material and thickness required for an insulating bra that will prevent patients from experiencing excessive heat loss and the associated cold/pain sensations in their breasts at cool room temperature. We determined these parameters by assessing which combinations restored tissue temperatures seen in the reconstructed breast closer to tissue temperatures seen in the natural breast. This heat transfer analysis was performed with geometry based on a representation of the statistical average breast given by the Regensburg Breast Shape Model from the Regensburg University of Applied Sciences. Two breast models were created for comparison: one for the natural breast, with layers for muscle, breast tissue, subcutaneous fat, and skin; and one for the reconstructed breast with layers for implant, muscle, subcutaneous fat, and skin. The results of this study suggest thicknesses for different bra fabric materials, as well as the potential for designing a safe active heating element. Because the study was conducted with the statistical average breast geometry, these results can be generalized - with caution - to design insulating bras for the general patient population. It would be prudent to further analyze the sensitivity of results to variations in the breast geometry and tissue properties for such future design efforts.